1. Field of the Invention
The present invention relates to fluorous triphasic reaction and separation processes and, especially, to the applications of these processes to the resolution of racemic or partially enantiopure organic compounds such as alcohols, amines, carboxylic acids and derivatives of carboxylic acids.
2. Description of Related Art
Resolutions of racemic organic compounds into their enantioenriched or enantiopure component enantiomers are an important and commonly used process in chemical, pharmaceutical, biotechnological, agricultural and other industries. In the pharmaceutical field, for example, racemic drugs are frowned upon because one enantiomer of a racemate typically predominately or exclusively induces the decided physiological or pharmacological effects. Accordingly, highly enantioenriched or enantiopure drug substances are almost always preferred over racemates.
Highly enantioenriched or enantiopure compounds are generally obtained by one of three basic strategies: 1) they can be prepared from other enantiopure compounds such as natural products by chemical synthesis; 2) they can be prepared from achiral compounds by asymmetric synthesis, or 3) they can be prepared from racemic compounds by resolution. Because many racemic compounds are commercially available or easily prepared, the resolution strategy is especially important. See, for example, J. Jacques, A. Collet, S. H. Wilen, Enantiomers, Racemates and Resolutions; Wiley: New York, 1981; E. L. Eliel, S. Wilen, Stereochemistry of Organic Compounds; Wiley-Interscience: New York, 1994, Chapter 7; and A. Collet, “Resolution of racemates: Did you say ‘classical’?,” Angew. Chem., Int. Ed. Eng., 37, 3229 (1998). However, resolutions can often be expensive, wasteful and environmentally unfriendly processes. The problem is especially acute for the general class of resolutions called kinetic resolutions, in which a mixture of a starting compound and a chemical derivative or product must be separated. This separation is often time consuming and expensive, especially when chromatography and related separation processes are used. Such processes often generate large amounts of waste solvent that must be disposed of or destroyed. Improvements in reaction and separation processes are therefore desirable.
Fluorous techniques for chemical synthesis have recently emerged as powerful new reaction and separation tools; see, for example, D. P. Curran, Stimulating Concepts in Chemistry; F. Vögtle, J. F. Stoddard and M. Shibasaki, Ed.; Wiley-VCH: New York, 2000, p. 25. Most fluorous techniques can be classified by the separation method employed. Processes such as fluorous biphasic reactions and more recently fluorous triphasic reactions are typical of liquid-liquid based separations. See, for example, I. T. Horvath, “Fluorous biphase chemistry,” Acc. Chem. Res. 31, 641 (1988). The present inventors have discovered that new fluorous triphasic reaction and separation processes provide powerful and practical new methods for chemical resolution and other processes.